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Investigating the potential of Shikonin as a novel hypertrophic scar treatment.

Fan C, Xie Y, Dong Y, Su Y, Upton Z - J. Biomed. Sci. (2015)

Bottom Line: Our results indicate that Shikonin preferentially inhibits cell proliferation and induces apoptosis in fibroblasts without affecting keratinocyte function.In addition, we found that the proliferation-inhibiting and apoptosis-inducing abilities of SHI might be triggered via MAPK and Bcl-2/Caspase 3 signalling pathways.Furthermore, SHI has been found to attenuate the expression of TGF-β1 in Transwell co-cultured "conditioned" medium.

View Article: PubMed Central - PubMed

Affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, 4059, Australia. c3.fan@connect.qut.edu.au.

ABSTRACT

Background: Hypertrophic scarring is a highly prevalent condition clinically and results from a decreased number of apoptotic fibroblasts and over-abundant production of collagen during scar formation following wound healing. Our previous studies indicated that Shikonin, an active component extracted from Radix Arnebiae, induces apoptosis and reduces collagen production in hypertrophic scar-derived fibroblasts. In the study reported here, we further evaluate the potential use of Shikonin as a novel scar remediation therapy by examining the effects of Shikonin on both keratinocytes and fibroblasts using Transwell® co-culture techniques. The underlying mechanisms were also revealed. In addition, effects of Shikonin on the expression of cytokines in Transwell co-culture "conditioned" medium were investigated.

Results: Our results indicate that Shikonin preferentially inhibits cell proliferation and induces apoptosis in fibroblasts without affecting keratinocyte function. In addition, we found that the proliferation-inhibiting and apoptosis-inducing abilities of SHI might be triggered via MAPK and Bcl-2/Caspase 3 signalling pathways. Furthermore, SHI has been found to attenuate the expression of TGF-β1 in Transwell co-cultured "conditioned" medium.

Conclusions: The data generated from this study provides further evidence that supports the potential use of Shikonin as a novel scar remediation therapy.

No MeSH data available.


Related in: MedlinePlus

Effects of SHI on NF-κB signalling pathway. HSF were treated with SHI (0, 1 and 3 μg/mL) for 1, 24 or 48 h. Expression of protein was measured using the Odyssey Infrared Imaging system. All experiments were performed 3 times using cells from three patients. Triplicate treatments were assessed in cells from each patient. The data was pooled as the percentage of the untreated control. Representative images of the western blots are presented. Quantitative data were pooled from experiments using cells 3 different patients. *p < 0.05 versus the untreated control
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Fig5: Effects of SHI on NF-κB signalling pathway. HSF were treated with SHI (0, 1 and 3 μg/mL) for 1, 24 or 48 h. Expression of protein was measured using the Odyssey Infrared Imaging system. All experiments were performed 3 times using cells from three patients. Triplicate treatments were assessed in cells from each patient. The data was pooled as the percentage of the untreated control. Representative images of the western blots are presented. Quantitative data were pooled from experiments using cells 3 different patients. *p < 0.05 versus the untreated control

Mentions: A large number of studies have reported that nuclear factor-kappaB (NF-κB) plays essential roles in regulating inflammation and apoptosis [24, 25]. NF-κB normally binds with its inhibitor I-κB in an inactive state in the cytoplasm [26]. Phosphorylation of I-κB kinase-α/β (IKK-α/β) leads to the phosphorylation and subsequently degradation of I-κB, thus inducing the phosphorylation of NF-κB [27]. Activated (phosphorylated) NF-κB translocates into the nucleus and then regulates the transcription of its target genes, such as IL-1 and BCL2 [28]. As illustrated in Fig. 5, expression of total IKK-α/β in HSF was attenuated when exposed to SHI at 3 μg/mL for 1 h compared to the control (p < 0.05). However, the expression of p-IKK-α/β remained at the same level compared to the control. Down-regulation of p-I-κB and up-regulation of p-NF-κB were observed in HSF when exposed to SHI at 3 μg/mL for 24 and 48 h compared to the control. This data indicates that SHI at 3 μg/mL activates the NF-κB signalling pathway in HSF.Fig. 5


Investigating the potential of Shikonin as a novel hypertrophic scar treatment.

Fan C, Xie Y, Dong Y, Su Y, Upton Z - J. Biomed. Sci. (2015)

Effects of SHI on NF-κB signalling pathway. HSF were treated with SHI (0, 1 and 3 μg/mL) for 1, 24 or 48 h. Expression of protein was measured using the Odyssey Infrared Imaging system. All experiments were performed 3 times using cells from three patients. Triplicate treatments were assessed in cells from each patient. The data was pooled as the percentage of the untreated control. Representative images of the western blots are presented. Quantitative data were pooled from experiments using cells 3 different patients. *p < 0.05 versus the untreated control
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4537585&req=5

Fig5: Effects of SHI on NF-κB signalling pathway. HSF were treated with SHI (0, 1 and 3 μg/mL) for 1, 24 or 48 h. Expression of protein was measured using the Odyssey Infrared Imaging system. All experiments were performed 3 times using cells from three patients. Triplicate treatments were assessed in cells from each patient. The data was pooled as the percentage of the untreated control. Representative images of the western blots are presented. Quantitative data were pooled from experiments using cells 3 different patients. *p < 0.05 versus the untreated control
Mentions: A large number of studies have reported that nuclear factor-kappaB (NF-κB) plays essential roles in regulating inflammation and apoptosis [24, 25]. NF-κB normally binds with its inhibitor I-κB in an inactive state in the cytoplasm [26]. Phosphorylation of I-κB kinase-α/β (IKK-α/β) leads to the phosphorylation and subsequently degradation of I-κB, thus inducing the phosphorylation of NF-κB [27]. Activated (phosphorylated) NF-κB translocates into the nucleus and then regulates the transcription of its target genes, such as IL-1 and BCL2 [28]. As illustrated in Fig. 5, expression of total IKK-α/β in HSF was attenuated when exposed to SHI at 3 μg/mL for 1 h compared to the control (p < 0.05). However, the expression of p-IKK-α/β remained at the same level compared to the control. Down-regulation of p-I-κB and up-regulation of p-NF-κB were observed in HSF when exposed to SHI at 3 μg/mL for 24 and 48 h compared to the control. This data indicates that SHI at 3 μg/mL activates the NF-κB signalling pathway in HSF.Fig. 5

Bottom Line: Our results indicate that Shikonin preferentially inhibits cell proliferation and induces apoptosis in fibroblasts without affecting keratinocyte function.In addition, we found that the proliferation-inhibiting and apoptosis-inducing abilities of SHI might be triggered via MAPK and Bcl-2/Caspase 3 signalling pathways.Furthermore, SHI has been found to attenuate the expression of TGF-β1 in Transwell co-cultured "conditioned" medium.

View Article: PubMed Central - PubMed

Affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, 4059, Australia. c3.fan@connect.qut.edu.au.

ABSTRACT

Background: Hypertrophic scarring is a highly prevalent condition clinically and results from a decreased number of apoptotic fibroblasts and over-abundant production of collagen during scar formation following wound healing. Our previous studies indicated that Shikonin, an active component extracted from Radix Arnebiae, induces apoptosis and reduces collagen production in hypertrophic scar-derived fibroblasts. In the study reported here, we further evaluate the potential use of Shikonin as a novel scar remediation therapy by examining the effects of Shikonin on both keratinocytes and fibroblasts using Transwell® co-culture techniques. The underlying mechanisms were also revealed. In addition, effects of Shikonin on the expression of cytokines in Transwell co-culture "conditioned" medium were investigated.

Results: Our results indicate that Shikonin preferentially inhibits cell proliferation and induces apoptosis in fibroblasts without affecting keratinocyte function. In addition, we found that the proliferation-inhibiting and apoptosis-inducing abilities of SHI might be triggered via MAPK and Bcl-2/Caspase 3 signalling pathways. Furthermore, SHI has been found to attenuate the expression of TGF-β1 in Transwell co-cultured "conditioned" medium.

Conclusions: The data generated from this study provides further evidence that supports the potential use of Shikonin as a novel scar remediation therapy.

No MeSH data available.


Related in: MedlinePlus